In silico screening of a chemical library based on pharmacophores for potential RAF-protein kinase inhibitors.

Varekamp, Jurriaan (2019) In silico screening of a chemical library based on pharmacophores for potential RAF-protein kinase inhibitors. Bachelor's Thesis, Pharmacy.

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Abstract

Rapidly accelerated fibrosarcoma (RAF-) protein kinases play an important role in the development of cancer, since they play an important role in the mitogen activated protein kinase (MAPK-) pathway. In this pathway they activate the ERK- and MEK-pathways leading to cell proliferation and cell survival. RAF-protein kinases exist of 3 proteins. These are ARAF, BRAF and CRAF. The most important of these ones is BRAF. This is because BRAF mutations are described in 40-70% of all melanomas. 95% of all these mutations is the BRAFV600E mutation. This mutation is able to continuously activate the ERK- and MEK-pathways leading to constant proliferation and survival of cells. Searching for compounds hat may inhibit these protein kinases in a chemical library through virtual screening is an easy and efficient way of sieving through multiple known compounds that can be reused for different diseases. This will also greatly decrease the research that is needed to distribute it as an actual drug to cancer patients, because some research has already been done on the compounds present in the chemical library. RAF-protein kinase inhibitors exist mostly of azoles or imidazoles, since these structures are able to bind to the ATP-pocket. Furthermore, nitrogen atoms are mostly present in side chains of known RAF-protein kinase inhibitors due to the fact they increase the binding affinity with the RAF-protein kinases.

Item Type:	Thesis (Bachelor's Thesis)
Supervisor name:	Groves, M.R. and Vilacha Madeira R Santos, J.F.
Degree programme:	Pharmacy
Thesis type:	Bachelor's Thesis
Language:	English
Date Deposited:	08 Jan 2020 10:12
Last Modified:	08 Jan 2020 10:12
URI:	https://fse.studenttheses.ub.rug.nl/id/eprint/21345

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